Year: 2018
Type: article
Abstract: MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here, we describe a neuroprotective function of miR-132, the miRNA most significantly downregulated in neurons in Alzheimer's disease. We demonstrate that miR-132 protects primary mouse and human wild-type neurons and more vulnerable Tau-mutant neurons against amyloid β-peptide (Aβ) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death. Similarly, miR-132 attenuates PHF-Tau pathology and neurodegeneration, and enhances long-term potentiation in the P301S Tau transgenic mice. The neuroprotective effects are mediated by direct regulation of the Tau modifiers acetyltransferase EP300, kinase GSK3β, RNA-binding protein Rbfox1, and proteases Calpain 2 and Caspases 3/7. These data suggest miR-132 as a master regulator of neuronal health and indicate that miR-132 supplementation could be of therapeutic benefit for the treatment of Tau-associated neurodegenerative disorders.
Source: Acta Neuropathologica
Institutions: Brigham and Women's Hospital, Harvard University, McLean Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Awards: MicroRNA regulation of early events in Alzheimer’s disease, NMDA receptor hypofunction contributes to the dendritic dysplasia in schizophreni, Aging in the Brain: Role of the Fibrous Proteins, NMDA receptor hypofunction contributes to the dendritic dysplasia in schizophreni, Aging in the Brain: Role of the Fibrous Proteins
OpenAlex ID: W2949187527